The activities of spermidine synthase and spermine synthase in mammalian cells will be measured under various physiological conditions which affect the growth rate. These aminopropyltransferases will be purified by conventional and affinity chromotography and their substrate specificity with respect to the aminopropyl acceptor determined. Possible inhibitors of these enzymes will be synthesized based on analogs of decarboxylated S-adenosyl-methionine and 5'-methylthioadenosine and transition-state analogs of the reactions. The effects of these inhibitors on polyamine content, cell growth and physiological responses will be tested. The levels of decarboxylated S-adenosylmethionine, the substrate for aminopropyltransferases, and of 5'-methylthioadenosine, an inhibitory product, will be measured by radioimmunoassay in extracts from cells treated with substances affecting growth rate and polyamine content. Finally the enzymatic reactions resonsible for the loss of the aminopropyl group from spermidine converting it to putrescine will be elucidated using as a model system hepatotoxin-treated rat liver in which this conversion is greatly enhanced.